ASBMB’s International Flavor

BY NICK ZAGORSKI

Although the American Society for Biochemistry and Molecular Biology is ostensibly an American-based enterprise, ASBMB, like the science it represents, is truly an international entity. Whether they are born or trained abroad, undertaking international collaborations or sabbaticals or just traveling to conferences outside the U.S., ASBMB members continually interact with the larger scientific world. Beyond even that, ASBMB counts among its 12,000 members a significant proportion of researchers who carry out first-rate basic research at institutions abroad. In recognition of this global reach, we present profiles of some of these international men and women of ASBMB.

Jennifer Martin

Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia

In the movies, destiny always seems to step in at the last possible instant. Such moments are usually not as timely in real life, although Jennifer Martin did have a cinematic experience at a pivotal point in her career.

She recently had completed her masters’ degree in pharmacy in Melbourne with Peter Andrews, where she had used computational tools to study opioid analgesics, and was about to board a flight on her way to the United Kingdom to begin her next career phase— although she wasn’t exactly sure what that career would be.

“I didn’t know whether I wanted to be a pharmacist or a scientist,” she says, “so I left it in the hands of fate. I applied for numerous scholarships and decided that if I was awarded a scholarship I would continue as a scientist, studying for a doctorate in structure-based drug design with Peter Goodford at Oxford University. If I missed out on a scholarship, I figured that I wasn’t destined to be a scientist, and I would instead work in England as a pharmacist.”

Having received only rejections, Martin seemed ready to pursue the latter option as she passed through security, but, right at the gate, the staff flagged her down. They informed Martin that the dean of her pharmacy college had requested she contact him urgently; she called from a public phone with her last twenty-cent piece and was told that she just had won a prestigious scholarship.

“Here I was, at a life-changing moment,” says Martin, “and I had no one to share it with because I had to board the plane.”

In another twist, the Laboratory for Molecular Biophysics where Goodford was based was almost entirely devoted to protein crystallography. As a result, Martin’s doctoral research combined both drug design and protein crystallography— the latter supervised by Louise Johnson— and her research has followed a similar path ever since.

Now an Australian Research Council laureate fellow and professor in structural biology at the University of Queensland’s Institute for Molecular Bioscience, where she has been since 1993 (previous stops included an appointment at Australia’s Bond University and a postdoc with John Kuriyan at Rockefeller University), Martin continues to focus on the relationship between protein structure and drug action. As someone who always has been interested in puzzles and how things piece together, teasing out this structure-function relationship is a perfect fit.

The Queensland Bioscience Precinct— the building that houses UQ’s Institute for Molecular Bioscience.

Much of Martin’s work centers on proteins involved in insulin signaling and diabetes, and her recent efforts have focused on understanding the regulation of SNARE proteins, which are involved in the insulin-stimulated trafficking of the GLUT4 glucose transporter. For instance, she discovered that the regulatory protein Munc18c can accelerate SNARE complex formation and vesicle fusion by binding to a short N-terminal peptide on the SNARE protein syntaxin4 and that this interaction is conserved in almost all SNARE systems.

Martin also recently was awarded a program grant from Australia’s National Health and Medical Research Council to work alongside cell biologists, metabolic scientists and clinicians to identify novel proteins associated with diabetes and to characterize these proteins at a structural and functional level.

In addition to her own group’s work, Martin has been instrumental in nurturing Australia’s structural biology presence through work on various scientific committees.

“Protein crystallography has grown tremendously in Australia since I first started my lab in 1993,” she says. “There were maybe six or seven groups back then, but today, that number has grown to over 40.”

The growth in protein crystallography is a welcome trend, especially considering Australia’s history in this field, adds Martin, who is a bit of a history buff. Australia’s first ever Nobel laureate was Lawrence Bragg in 1915. He won the award at age 25 alongside his father, William Bragg, for solving the first ever x-ray crystal structure (of sodium chloride).

And, because of the efforts of Martin and her colleagues, today’s Australian and New Zealander crystallographers can achieve their own breakthroughs much more easily, thanks to the 2007 opening of the Australian Synchrotron in Victoria. Previously, synchrotron data measurement required time-consuming and expensive trips to the U.S., Japan or Europe, but now, researchers have a much more convenient destination, as well as a centralized area where the burgeoning crystallography community can converge.

Of course, some part of Martin may miss the frequent airline travel; after all, you never know what kind of life-changing experience you might have while waiting to board a plane.

Andrej Shevchenko

A decade ago, if you asked Andrej Shevchenko his opinion on lipids, his answer would not be too flattering. “I was a 100 percent protein guy,” he says, “and, as an analytical protein chemist, lipids were synonyms for trouble. Whenever I saw mass spectra that didn’t look right, I suspected that the scientists did not delipidate their samples fully.”

However, over the past few years, Shevchenko, a group leader at the Max Planck Institute of Molecular Cell Biology and Genetics, one of the newest of the 80 research institutes set up by the Max Planck Society, has come around. Lipids are no longer just greasy and cloudy contaminants or solvents for hydrophobic proteins; they’re integral biological molecules that warrant their own study.

So, while he continues to work on protein analysis, for example, identifying protein interaction networks in yeast or developing programs that can characterize the proteomes of organisms that are related very distantly to organisms with sequenced genomes, Shevchenko has begun to apply his skills to better quantify the lipid composition of various organelles, cells and tissues.

And, at the MPI-CBG, Shevchenko has found an ideal home to pursue these ideas. Surrounded by top-level cell biologists and an environment that encourages exploratory research, Shevchenko continually is moving from one exciting project to the next, adding his analytical mind to various collaborative efforts.

Born and educated in Russia, Shevchenko developed strong interests in both organic chemistry and analytical chemistry in school and gravitated naturally toward mass spectrometry analysis. In 1994, he moved to the European Molecular Biology Laboratory in Heidelberg, first, as a visiting scientist with noted proteomicist Matthias Mann, and, later as a staff scientist.

“However, they don’t have tenured appointments at the EMBL, so after a few years, I had to move on,” he notes. Fortunately, at that time, Max Planck was setting up their new CBG campus in the former East German city of Dresden, and several of Shevchenko’s former EMBL colleagues were slated to join. “And, they asked if I would be interested to come with them and set up a bioanalytics lab,” he says.

Shevchenko notes one of his big fears was that he would end up doing proteomic analysis of a primarily technical or service nature, which would eventually become boring; however, given this invitation by scientists he knew and respected, his decision was a “no-brainer.”

Situated near Germany’s border with the Czech Republic and Poland, the MPI-CBG is a highly interactive and dynamic institute that hosts scientists of more than 35 nationalities, and, with that broad diversity and the fact that all institute meetings and seminars are held in English— “or what we believe to be English,” Shevchenko says jokingly— one may sometimes forget where they are.

The MPI-CBG building at night.

Which would be a shame, Shevchenko adds, because the surrounding city of Dresden is quite energetic and worth visiting.

Of course, there is plenty of energy in the lab as well, as can be expected from a field like proteomics that has been rapidly advancing; technical issues that were bottlenecks just two years ago have been resolved, notes Shevchenko, who can follow advances closely as an editorial board member for the ASBMB journal, Molecular and Cellular Proteomics.

“The “omic” sciences are becoming much more quantitative than descriptive now,” he says, “and we are really beginning to understand the molecular aspects of these proteins, complexes or networks that we study. In addition to pure numbers, proteomics also has moved forward by now being able to track measurements in both time and space, which is especially exciting.”

Shevchenko is hoping to use these new advances to tackle an ambitious project aimed at marrying lipidomics with developmental biology. As organisms grow and develop from a single cell, newly differentiated tissues require their own unique membrane lipid composition, and Shevchenko hopes to characterize these tailored changes to better understand how inherited defects in lipid metabolism cause disease.

And, to think, a few years ago, lipids was just another dirty word.

Anthony H. Futerman

Weizmann Institute of Science, Rehovot, Israel

Although he often dreamed of pursuing an academic career during his youth in England, Anthony H. Futerman notes that the deal was officially sealed when he got a hold of a certain iconic biochemistry textbook.

“Blame Lehninger,” he says. “I was given a copy of that book by my high school teacher, and I found it so fascinating that, right then and there, I decided to become a biochemist, at the age of 16,” he says. Futerman enjoyed the book so much, in fact, that he purchased his own copy two years later when he went to the University of Bath for undergraduate studies, a copy he still displays proudly on his office shelf at the Weizmann Institute of Science.

Fittingly, a book also would play a prominent role in leading Futerman to this renowned scientific institution in Rehovot, Israel. He found an article about the Weizmann Institute in the Encyclopedia Britannica when he was young, and, after his university adviser mentioned that Weizmann might be a good destination for graduate school, Futerman decided that was where he wanted to go.

Three decades later, Futerman, now the Joseph Meyerhoff professor of biochemistry, is still going strong at Weizmann— although he did travel abroad for a short postdoctoral fellowship with Richard Pagano at the Carnegie Institute in Baltimore— studying the biochemistry of sphingolipids, an important lipid class with functions in both membrane biology and cell signaling, and their role in lysosomal storage diseases like Gaucher and Tay Sachs.

“It’s not too surprising, since historically, education and Jewishness always go together, but there is a wonderful scientific culture here at Weizmann,” Futerman notes of this somewhat unusual research university that solely offers graduate and postdoctoral education. “And that was even before we had our first Nobel Prize winner this past year (Ada Yonath). But, I think that helped make us even more visible on the international scientific map.”

Add the fact that Futerman, along with about half of Weizmann’s 250 international faculty members, gets to live on the picturesque campus and only has a short walk to his lab, and one can understand the appeal.

The only downside is that Futerman is the sole lipid specialist at Weizmann (his colleague and fellow international ASBMB member Mordechai Liscovitch recently passed away), although Futerman has remedied that through numerous external collaborations with labs all over the world, such as Al Merrill’s group at Georgia Tech, and frequent travel to meetings.

A view of the Weizmann Institute campus featuring the futuristic Koffler nuclear accelerator in the background.

Futerman’s graduate studies centered on GPI-anchored proteins, but after completing his degree, he attended a Federation of the Societies of Biochemistry and Molecular Biology (FEBS) summer school and spoke to a number of lipid scientists who stimulated his interests in lipid cell biology. This eventually led to his postdoctoral position with Pagano as well as his first taste of sphingolipid research.

Since returning to Israel in 1990, Futerman’s lab has focused on two main areas: understanding the mechanistic basis for lysosomal storage diseases to identify new therapeutic applications and characterizing the biosynthesis of sphingolipids, particularly ceramides. His group has brought forth some important contributions in this arena, such as determining the first crystal structure of the enzyme mutated in Gaucher disease, acid β-glucosidase (together with Weizmann colleagues Joel Sussman and Israel Silman) and discovering that glycosphingolipids can regulate calcium homeostasis in neurons.

Currently, he’s looking at how the accumulation of specific sphingolipid species translates to specific diseases and phenotypes, as well as examining how the length and saturation of sphingolipid acyl chains— the molecular tails that range from 14 to 32 carbons long— affect function in signaling activity and membrane fluidity.

Futerman also has been a member of the Journal of Biological Chemistry editorial board since 2000. “Since I started, I’ve noticed the board has been becoming more international, which I think is very important,” he says. “The JBC may be American-published, but in looking at the articles each week, it’s clearly an international journal, and it’s nice for these authors to know that their international colleagues are involved in the selection process.”